The Gastrointestinal (Gl) Cancer Program (Program #6), one of the original programs of the Kimmel Cancer Center at Jefferson, is a multidisciplinary program composed of 25 full and 5 associate members representing 8 departments within Jefferson Medical College (Pathology; Cancer Biology; Family Medicine; Internal Medicine; Medical Oncology; Pharmacology; Radiology; Surgery), the Christiana Care Health System (Helen F. Graham Cancer Center), and Drexel University, whose over-arching goal is to define fundamental mechanisms underlying Gl malignancies which can be translated into diagnostic and therapeutic innovations for managing cancer in patients and populations. Their work is supported by ~$7.7M in peer-reviewed funding, representing an increase of -75% from $4.4M during the past funding period. Also, program members have published 561 papers, representing almost a doubling compared to the previous funding period. Of those, >17% were intra-programmatic, representing a tripling of the previous rate, and >16% were inter-programmatic. Program members pursue parallel efforts organized along organ based disease processes from discovery through translation to clinical development and application. Members employ common and collaborative experimental paradigms with the goals of (1) defining previously unappreciated molecular, genetic, and epigenetic mechanisms underlying Gl organ-based tumorigenesis, (2) translating defined mechanisms into novel in vitro and in vivo tools to improve prevention, early detection, prognosis, prediction, and risk-stratification in Gl malignancies, (3) defining molecularly targeted therapeutic approaches for cancer prevention, treatment, and control, (4) advancing novel laboratory discoveries into development for clinical trials, and (5) advancing clinically successful diagnostic and therapeutic trials into evidence-based practice for cancer prevention and control across populations. In that context, enrollment of patients in Gl cancer-based clinical trials has increased ~15-fold compared to the past funding period. Members are interactive and cohesive and, under the direction of Program Leaders, coordinate research planning and new research directions with other research programs in the Cancer Center.